Oxidative Stress

Oxidative stress is caused by an imbalance between the production of reactive oxygen species (ROS) and a biological system's ability to readily detoxify reactive intermediates or easily repair the resulting damage. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including proteins, lipids and DNA.

In humans, oxidative stress is involved in many diseases, such as, atherosclerosis, Parkinson's disease, Myocardial Infarction, Alzheimer's disease and Chronic Fatigue syndrome. Oxidative stress is thought to be linked to certain cardiovascular diseases because oxidation of LDL in the vascular endothelium is a precursor to plaque formation.

Short-term oxidative stress may be beneficial in that ROS can trigger apoptosis and remove damaged cells from an organism. Reactive oxygen species can also be beneficial in the prevention of aging, they are used by the immune system as a way to attack and kill pathogens and ROS are also used in cell signaling processes (redox signaling).

One source of reactive oxygen under normal conditions in humans is the leakage of activated oxygen from mitochondria during oxidative phosphorylation. Other enzymes capable of producing superoxide are xanthine oxidase, NADPH oxidases and Cytochromes P450. Hydrogen peroxide is produced by a wide variety of enzymes including several oxidases. Disturbances in the normal redox state of cells can cause toxic effects through the production of peroxides and free radicals that damage all components of the cell, including DNA, lipids and proteins.

Selected Oxidative Damage Biomarkers

1. DNA damage

8-OHdG:

In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, is the most frequently detected and studied DNA breakdown product (1). Upon DNA repair, 8-OHdG is excreted in the urine. Several studies have indicated that urinary 8-OHdG is not only a biomarker of generalized, cellular oxidative stress but might also be a risk factor for cancer, atherosclerosis and diabetes (2-4).

8-OHdG is typically measured in both urine and serum/plasma samples. 8-OHdG is a hydroxyl radical-damaged guanine nucleotide that has been excised from DNA by endonuclease repair enzymes. Since repair is known to normally occur quickly and efficiently, the amount of excised DNA adducts in urine directly reflects the amount of damage within the entire body.

Lipid peroxidation refers to the oxidative degradation of lipids. It is the process whereby free radicals take up electrons from the lipids in cell membranes, resulting in cell damage. It most often affects polyunsaturated fatty acids, because they contain multiple double bonds that contain methylene-CH2- groups that possess especially reactive hydrogen groups.

8-epi-PGF2a (F2-Isoprostane) is the free Radical catalyzed non-enzymatic oxidation product of arachidonic acid (5). Peroxidation of arachidonic acid occurs in cellular membranes and lipoproteins (i.e. LDL). The damaged lipid peroxide is excised from the cell wall into the serum and then excreted in urine. Unlike the reactive aldehydes, once isoprostanes are formed they are chemically stable and can be accurately measured in urine.

3. Protein Damage

Nitrotyrosine:

Nitrotyrosine is formed in tissue or blood proteins after exposure to nitrosating and/or nitrating agents. Reactive nitrogen species such as peroxynitrite can nitrate specific amino acids, whether free or protein bound, and nitrotyrosine is believed to be one marker of this reaction (6,7). Nitrotyrosine has been widely studied and has been associated as a biomarker for several inflammatory disorders, such as Alzheimer's disease, ALS, asthma, atherosclerosis, cardiovascular disease, COPD, coronary artery disease, Crohn's, cystic fibrosis, diabetes, hypercholesterolemia, lung cancer, lung injury, MS, myocardial inflammation, osteoarthritis and rheumatoid arthritis.